Variant chr21-46111447-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_001849.4(COL6A2):c.-27-3C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,414,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

COL6A2
NM_001849.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.9990

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.266

Variant links:

Genes affected

COL6A2 (HGNC:2212): (collagen type VI alpha 2 chain) This gene encodes one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The product of this gene contains several domains similar to von Willebrand Factor type A domains. These domains have been shown to bind extracellular matrix proteins, an interaction that explains the importance of this collagen in organizing matrix components. Mutations in this gene are associated with Bethlem myopathy and Ullrich scleroatonic muscular dystrophy. Three transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

COL6A2 links:

LOC124905043 (HGNC:):

LOC124905043 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

PP5

Variant 21-46111447-C-G is Pathogenic according to our data. Variant chr21-46111447-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1184572.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
COL6A2	NM_001849.4 linkuse as main transcript	c.-27-3C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000300527.9
COL6A2	NM_058174.3 linkuse as main transcript	c.-27-3C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000397763.6
LOC124905043	XR_007067910.1 linkuse as main transcript	n.585G>C	non_coding_transcript_exon_variant	1/2
COL6A2	NM_058175.3 linkuse as main transcript	c.-27-3C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9 linkuse as main transcript	c.-27-3C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_001849.4	P1	P12110-1
COL6A2	ENST00000397763.6 linkuse as main transcript	c.-27-3C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5	NM_058174.3		P12110-2
COL6A2	ENST00000436769.5 linkuse as main transcript	c.-27-3C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2
COL6A2	ENST00000409416.6 linkuse as main transcript		upstream_gene_variant	5			P12110-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

242066

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132076

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1414928

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

704646

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000388

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000187

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Ullrich congenital muscular dystrophy 1A

Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Genomics England Pilot Project, Genomics England

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.63

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.41

Position offset: 11

DS_AL_spliceai

0.63

Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over